Interactions between antibodies and chondrocytes.
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Biomedical subjects
Publications and source records attributed to T D Cooke.
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Netilmicin, a new aminoglycoside antibiotic, was used to treat 19 patients with urinary tract infection and 5 with systemic infection. The causal organisms were Escherichia coli (in 2), Klebsiella pneumoniae (in 4), Serratia marcescens (in 12) and Pseudomonas aeruginosa (in 7); 1 patient was infected with two of these organisms. All the isolates of causal organisms except one of Serratia were initially sensitive to netilmicin but many were resistant to other aminoglycosides. Sixteen of the urinary tract infections responded to netilmicin therapy, although relapse occurred in three patients. Two of the three patients with musculoskeletal infection responded to combined therapy with surgery and netilmicin; the other patient responded to the same regimen but with carbenicillin added. Netilmicin cured pneumonia in one patient but failed in the other patient with pneumonia, who had leukemia. Superinfection occurred in five patients with urinary tract infection. Adverse reactions to netilmicin were minor. Netilmicin may prove to be a useful agent, particularly for infections due to multiresistant Klebsiella or Serratia, or when prolonged aminoglycoside therapy is required.
Immunoelectron microscopy for IgG and IgA was combined with plain electron microscopy and light microscopy to study a variety of articular collagenous tissues from 14 cases of classic rheumatoid arthritis. Numerous extensive aggregates of IgG and IgA positive material were found widely spread in locations that coincided with immunofluorescent staining for these immunoglobulins and B1c. This Ig positive material is thought to represent deposits of immune complexes. As great and greater amounts were seen in fibrocartilage menisci as in hyaline cartilage. A single specimen of disease tendon was also positive. Severe pathologic changes of the matrix characterized by loss of normal morphology, alterations in collagen, and overall reduced density were observed in regions of aggregate deposition with a consistent replacement and disappearance of collagen in the locale of the aggregates themselves. Polymorphonuclear cells in regions of degraded hyaline and tendon matrix were seen to have phagocytosed aggregates. These data give some credence to a direct role of immune aggregates in rheumatoid arthritis articular collagenous tissues in disease pathogenesis.
The inflammatory role of immune complexes trapped in joint collagenous tissues has been investigated. Joint collagenous tissues obtained from rabbits with antigen-induced arthritis generated mediators of acute inflammation when incubated with fresh normal rabbit serum as a source of complement. The role of trapped immune complexes in chronic inflammation was also studied by the surgical insertion of menisci, obtained from arthritic and control joints, into the suprapatellar pouches of previously immunized or naive recipient animals. It was shown that when immune complex containing menisci were inserted into immune rabbits, a chronic inflammatory capsule developed around the donor tissue, reminiscent of the inflammatory pannus seen in rheumatoid cartilage. Normal menisci and immune complex containing menisci inserted in naive animals developed capsules rich in fibroplasts and collagen fibres. Since we have previously shown the presence of immune complexes in the great majority of joint collagenous tissues obtained from patients with rheumatoid arthritis, our results suggest that these complexes may play a role in the formation of pannus, which constitutes a major mechanism responsible for cartilage destruction.
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Ninety-three patients with a variety of joint diseases were studied for evidence of immune complexes in articular collagenous tissues. Frozen sections of freshly obtained biopsies of hyaline articular cartilage and menisci were stained with fluoresceinated monospecific antisera for evidence of human immunoglobulins (IgG, IgM,IgA) and the beta1c component of complement. The criterion for the presence of complexes was the staining of two or more immunoglobulins and beta1c in an identical location of sequentially cut sections. Of the 42 patients with rheumatoid arthritis (RA) 83% were positive by this criterion. In those with classic RA the incidence was 92%. Sixteen patients with fresh joint trauma or nonarthritic disease had negative findings. Among 26 patients with noninflammatory disease, 4 of 8 with polyarthritis whose features suggested primary degeneration, 1 of 11 patients with secondary degenerative arthritis, and a single case of synovial osteochondromatosis had positive findings. Among 9 patients with miscellaneous inflammatory arthritides, all of 3 with psoriatic arthritis were negative; however 2 of 6 with other inflammatory arthritides were positive. The findings in classic RA suggest that immune complexes are deposited in the articular collagenous tissues. The persistence of these complexes may play a significant role in the chronicity of the synovitis.
The earliest and most severe changes in articular collagenous tissues (ACT) occur within 24 hours of antigen challenge and are associated with and are possibly secondary to maximal immune complex deposition in ACT surfaces. The immuno-electron microscopic (immuno-em) staining characterizes the ferritin as aggregates with antibody and suggests its occurrence and deposition as a preformed immune complex. These data indicate a direct interaction between immune complexes and collagenous matrix which could relate to both antigen persistence and chronicity of the immune response. The changes described in this model have features in common with rheumatoid disease and suggest the potential for similar mechanisms of cartilage degradation.